Inheritance

WAS is an X-linked recessive trait which means that boys who inherit the abnormal gene are affected by the disease whereas girls who inherit the gene are healthy carriers of the disease. Female carriers have an abnormal WASP gene on one X chromosome and a normal gene on their other X chromosome. The normal gene allows the carrier to produce WASp, thereby protecting the carrier from having Wiskott-Aldrich Syndrome. Boys, on the other hand have only one X chromosome and when they inherit a mutated gene, their WASp production is deficient or absent causing WAS. Two thirds of the patients inherit the disease from the mother who is a healthy carrier of the abnormal WAS gene. In a third of the patients the mother is not a carrier and there was a new mutation of the gene in the affected male.

Boys born to a mother with the abnormal WASP gene have a 50% chance of inheriting the abnormal gene and having the disease and girls born to this mother have a 50% chance of inheriting the abnormal gene and becoming a carrier. All boys born to a father with WAS will be healthy whereas all of his daughters will be carriers of the disease. Families with an X-linked recessive disorder often have affected males but rarely have affected females in each generation. Families may have a history of brothers, maternal uncles being affected by the disease. Girls are very rarely affected. This happens when their normal X chromosome is inactivated resulting in a lack of WASp.

Inheritance patterns - example 1

In this example, a man with an X-linked recessive condition has two unaffected daughters who each carry one copy of the gene mutation, and two unaffected sons who do not have the mutation.

Courtesy: Genetics Home Reference

Inheritance patterns - example 2

In this example, an unaffected woman carries one copy of a gene mutation for an X-linked recessive disorder. She has an affected son, an unaffected daughter who carries one copy of the mutation, and two unaffected children who do not have the mutation.